TTF-1 POSITIVE THYROID-LIKE PAPILLARY WILMS’ TUMOR.

M. Bisceglia (1), G. Lastilla (2), N. Santoro (3), F. De Leonardis (3), and C. Galliani (4).

Department of Pathology, IRCCS-Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy (1); Department of Pathology, Polyclinic Hospital, Bari, Italy (2); Department of Pediatric Medicine, Polyclinic Hospital, Bari, Italy (3); Department of Pathology, Cook Children’s Medical Center, Fort Worth, Texas, USA (4).

• We reported elsewhere (1-2) on the results of a general study of TTF-1 expression in Wilms’ tumor (WT) and some congeners.

• Eight of 48 WTs so studied proved to be positive for TTF-1.

One of these eight positive cases (case 16 of the series (2) was particularly intriguing to us both clinicopathologically and immuno- histochemically.

Introduction

A 2 year, eight month-old male underwent radical left nephrectomy at the Polyclinic Hospital, Bari,

Italy. • The 200 g, 10.5 x 6 x 5 cm nephrectomy specimen

contained a 6 cm in diameter, demarcated tumor arising from the lower pole.

• The tumor invaded the capsule, pyelocalyceal system and renal sinus.

• Bulky metastatic disease affected 3 hilar and 2 aorto-caval lymph nodes.

Case Report and Design

• Histopathologically, the lower pole mass and the bulky lymphnode metastatic deposits were predominantly epithelial nephroblastoma with florid papillary features and many psammoma bodies.

• The epithelial component exhibited a striking thyroid-like appearance, including tiling of tumor cells, variable nuclear clearing, nuclear grooves in the primary, and rare nuclear pseudoinclusions in the metastasis.

• Foci of conventional triphasic WT, and perilobar nephrogenic rests, interdigitating with adjacent parenchyma, were also present in the primary.

Primary tumor

Lymph node metastasis

Sections of the primary WT and a lymph node metastasis showing a predominantly epithelial pattern of proliferations (metastasis was exclusively epithelial) were selected for further study, particularly to assess the expression of WT1 and TTF-1, in conjunction with other immunohistochemical markers.

• The primary WT was positive for both WT1 and TTF-1

(the former only focal in blastema and early epithellial components of triphasic foci), while the metastasis was WT1 negative and TTF-1 positive.

• Both the primary and the metastasis showed diffuse expression of CK/34betaE12 and CK19, focal S-100 protein cytoplasmic positivity, CD10 luminal cell surface positivity, and focal cytoplasmic expression of thyroglobulin, an immunoprofile mostly consistent with thyroid differentiation (3a).

• CD56, a consistently positive marker in WT, was negative in both the primary and the metastasis.

Results

Primary tumorTTF-1 TTF-1

WT1 Thyroglobulin

Lymph node metastasis

TTF-1 WT1

CK19 CD10

Primary tumor(nephrogenic rests)

WT1

WT1

Morphologically there were areas of this tumor which were even evocative of a "translocation" renal cell carcinoma of Xp11.2 type.

However, the location of the primary, its essentially triphasic nature, the presence of nephrogenic rests and the age of the patient were all consistent with a primary WT.

A papillary pattern and concentric calcospherites are not uncommon in WT and there was no evidence of a co-existing thyroid carcinoma (also, papillary thyroid carcinoma in children is a typically indolent disease).

Among the notoriously heterogeneous morphologic and immunohistochemical spectrum of nephroblastomas (3b), we identified a thyroid-like, strongly TTF-1 positive tumor with a florid papillary pattern and psammoma bodies.

This peculiar morphology in association with immunopositivity for TTF1 could easily lead to erroneous interpretation.

Clinicopathological correlation is essential to avoid the potential for confusion.

Conclusion.

• The patient received chemotherapy according to SIOP standard protocol for

stage III nephroblastoma.

• The patient is alive 21 months after nephrectomy

Follow-up

1. Bisceglia M, Ragazzi M, Galliani C., Lastilla G, and Rosai J. TTF-1 expression in nephroblastoma: analysis of a series. Atti Congresso Nazionale SIAPEC-IAP, Bari, September 25-27, 2008.

2. Bisceglia M, Ragazzi M, Galliani C, Lastilla G, Rosai J. TTF-1 expression in nephroblastoma. Am J Surg Pathol 2008, in press.

3. Rosai J. Rosai and Ackerman’s Surgical Pathology. 9th edition, Vol 1, Mosby: New York, 2004; 532-542 (a); 1240-1245 (b).

References